The overall objective of the proposal is to obtain important information concerning the nature, control and effects of the gastrointestinal hormone, secretin. This hormone is selected for study for several reasons. Recognized as a mediator of gastrointestinal alkaline secretions, an etiologic role has been suggested for secretin in the symptomatology of WDHA syndrome associated with an endocrine tumor of the GI tract. Also secretin has been suggested as an inhibitory modulator of gastric acid secretion. Until recently physiological concepts of these actions of secretin and others were based on studies such as bioassays utilizing indirect measurement of limited sensitivity and specificity. This request proposes to study secretin peptides contained in intestinal mucosa and released into the circulation by intraduodenal acidification utilizing chromatographic and specific, sensitive radioimmunoassay techniques. The secretin content of gastric and small intestinal mucosa and sera obtained during fasting and stimulated conditions will be determined utilizing healthy human and canine subjects. Values obtained will be compared and contrasted with those from studies of conditions associated with gastric acid hypersecretion (Zollinger-Ellison syndrome and massive small bowel resection) and hyposecretion (histamine-fast achlorhydria). In order to evaluate the pathophysiologic role of secretin in the WDHA syndrome, sera and metastatic tissues will also be assayed for secretin content. Immunochemical heterogeneity of secretin from the mucosa and circulation will be characterized by gel filtration chromatography. Activities to improve the secretin immunoassay will be continued; specific plans for improvement in antibody affinity, further documentation of antibody specificity and improvement of radiosecretin purity with increased specific activity will be accomplished.